Biologics have immense commercial potential. However, developing successful candidates can feel like looking for a needle in a haystack. Research, development, manufacturing, and clinical testing are limited by substantial time and cost considerations. But what if you could identify a higher quantity of quality hits in a fraction of the time and with a fraction of the resources of traditional antibody discovery processes?
Hurdles in Monoclonal Antibody Discovery
Antibody treatments are one category of biologics that are highly desired and commercially viable but difficult to develop. Over the last 25 years, the market for monoclonal antibodies (mAbs) has boomed and is projected to generate a staggering $300 billion in global revenue by 2025.1 Pharma players are responding to this massive demand by entering into a highly competitive antibody discovery (ABD) field, facing traditional development processes that are arduous, time-consuming, and resource-intensive—all without any assurance of results.
Drawbacks of Conventional Discovery Approaches
One conventional mAb production technique involves fusing antibody-producing B cells with immortalized cancer cells to create hybridoma cell lines. Hybridoma technology was the first method developed for mAb production, but a large proportion of the original B cell repertoire die at fusion,2 greatly reducing efficiency and excluding potential candidates. In addition, it takes roughly 12 weeks to move from therapeutic target to lead molecule which significantly limits the speed of development.
A second discovery method removes the need for fusion by sequencing B cells to identify and isolate promising antibodies. While halving the time to lead molecule to six weeks, B cell sequencing doesn’t provide information needed to select the best cells after isolation and sequencing. The cells that are selected to move forward into development need multiple time-consuming assays to understand their functional characteristics.
The Beacon Accelerates Antibody Discovery
Enter the Beacon. The Bruker Cellular Analysis Beacon® Optofluidic System shortens the selection process by putting function first, helping to narrow down biotherapy candidates that evade classical discovery techniques. This compact and scalable platform replaces well plates with OptoSelect® chips that move cells with light patterns. OptoSelect® chips contain nanoliter-sized Nanopen® chambers that enable rapid screening of up to 40,000 single B cells with multiple assays in a single workflow.
By isolating and assaying a single cell in its own chamber, the Beacon® Opto® Plasma B Discovery workflow fuels an accelerated, accurate down-selection of lead molecules by functional profiling. Removing the need for laborious bacterial cloning and time-consuming gene synthesis shortens the antibody discovery timeline from three months to less than one week. All in all, a miniaturized, efficient process lightens the load on lab resources, hands-on time, and helps minimize waste.
Tackling Difficult Targets
By moving functional profiling upfront, the Opto® Plasma B Discovery Workflow gives laboratories all the information they need to make informed lead molecule selection decisions quickly. Profiling assays can even be adapted to target cell surface receptors in difficult targets like G protein-coupled receptors (GPCR) and ion channels by using antigen-expressing cells to screen against the native antigen.
Compared to hybridoma, Beacon® can reveal 10x more quality hits against difficult transmembrane targets and slash mAb discovery time to just five days.
Breaking Down Barriers
Monoclonal antibody discovery will continue to be a complex process. With Beacon’s function-first workflow, labs can discover more candidates, faster, opening up a new world of possibilities for biologics and human health.
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- Lu, RM, Hwang, YC, Liu, IJ, et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci. 2020;27(1), 1-30. https://doi.org/10.1186/s12929-019-0592-z
- Pedrioli, A, & Oxenius, A. Single B cell technologies for monoclonal antibody discovery. Trends in Immunology. 2021;42(12), 1143-1158.